Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating and multifactorial disease characterized by a wide range of symptoms that severely impact all aspects of life. Despite its significant prevalence, ME/CFS remains understudied and lacks standardized diagnostic criteria and effective treatments. This review aims to provide a comprehensive overview of ME/CFS, discussing its symptoms, severity, diagnostic criteria, causes, and pathophysiology. **Symptoms and Severity:** ME/CFS is characterized by post-exertional malaise (PEM), where exertion leads to a prolonged period of fatigue and reduced stamina. Patients often experience cognitive and physical impairments, with symptoms varying widely among individuals. The severity of ME/CFS can be categorized into four levels: mild, moderate, severe, and very severe, each with distinct impacts on daily activities and quality of life. **Diagnostic Criteria:** There is no universally accepted clinical criteria for ME/CFS, making diagnosis challenging. Different diagnostic criteria exist, but they often rely on symptom-based exclusion of other disorders. PEM is considered a key diagnostic feature, though its severity varies widely. The disease is often diagnosed late, and the process can be prolonged due to the lack of uniform diagnostic criteria. **Causes and Triggers:** ME/CFS is believed to have a multifactorial origin, involving genetic predispositions and environmental triggers such as viral infections. Genetic studies have shown potential links between ME/CFS and specific gene polymorphisms, but the exact mechanisms are still not fully understood. Viral infections, particularly herpesviruses like Epstein-Barr virus (EBV), are often implicated as triggers, with evidence suggesting that reactivation of latent viruses can lead to the development of ME/CFS. **Pathophysiology:** The pathophysiology of ME/CFS involves a complex interplay of immune dysregulation, chronic inflammation, gut dysbiosis, and metabolic disturbances. Patients often exhibit gut inflammation and changes in the gut microbiome, leading to systemic inflammation. Chronic inflammation and redox imbalances contribute to oxidative stress and nitrosative stress, which further exacerbate symptoms. Vascular changes, including endothelial dysfunction and autonomic dysfunction, are also common, leading to vasoconstriction and hypoperfusion. Hypercoagulation and the presence of microclots in the circulation are hypothesized to play a significant role in the pathology of ME/CFS. **Conclusion:** ME/CFS is a complex and multifactorial disease that requires a holistic approach to diagnosis, research, and treatment. The lack of standardized diagnostic criteria and effective treatments highlights the need for further research to better understand the disease's multifactorial origins and develop more effective therapeutic strategies.Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating and multifactorial disease characterized by a wide range of symptoms that severely impact all aspects of life. Despite its significant prevalence, ME/CFS remains understudied and lacks standardized diagnostic criteria and effective treatments. This review aims to provide a comprehensive overview of ME/CFS, discussing its symptoms, severity, diagnostic criteria, causes, and pathophysiology. **Symptoms and Severity:** ME/CFS is characterized by post-exertional malaise (PEM), where exertion leads to a prolonged period of fatigue and reduced stamina. Patients often experience cognitive and physical impairments, with symptoms varying widely among individuals. The severity of ME/CFS can be categorized into four levels: mild, moderate, severe, and very severe, each with distinct impacts on daily activities and quality of life. **Diagnostic Criteria:** There is no universally accepted clinical criteria for ME/CFS, making diagnosis challenging. Different diagnostic criteria exist, but they often rely on symptom-based exclusion of other disorders. PEM is considered a key diagnostic feature, though its severity varies widely. The disease is often diagnosed late, and the process can be prolonged due to the lack of uniform diagnostic criteria. **Causes and Triggers:** ME/CFS is believed to have a multifactorial origin, involving genetic predispositions and environmental triggers such as viral infections. Genetic studies have shown potential links between ME/CFS and specific gene polymorphisms, but the exact mechanisms are still not fully understood. Viral infections, particularly herpesviruses like Epstein-Barr virus (EBV), are often implicated as triggers, with evidence suggesting that reactivation of latent viruses can lead to the development of ME/CFS. **Pathophysiology:** The pathophysiology of ME/CFS involves a complex interplay of immune dysregulation, chronic inflammation, gut dysbiosis, and metabolic disturbances. Patients often exhibit gut inflammation and changes in the gut microbiome, leading to systemic inflammation. Chronic inflammation and redox imbalances contribute to oxidative stress and nitrosative stress, which further exacerbate symptoms. Vascular changes, including endothelial dysfunction and autonomic dysfunction, are also common, leading to vasoconstriction and hypoperfusion. Hypercoagulation and the presence of microclots in the circulation are hypothesized to play a significant role in the pathology of ME/CFS. **Conclusion:** ME/CFS is a complex and multifactorial disease that requires a holistic approach to diagnosis, research, and treatment. The lack of standardized diagnostic criteria and effective treatments highlights the need for further research to better understand the disease's multifactorial origins and develop more effective therapeutic strategies.