The article discusses the growing global burden of liver steatosis associated with metabolic diseases, emphasizing its progression to more severe liver damage and increased risk of cardio-metabolic diseases and cancer. The terminology has evolved from "nonalcoholic fatty liver disease" (NAFLD) to "metabolic dysfunction-associated fatty liver disease" (MAFLD) and finally to "metabolic dysfunction-associated steatotic liver disease" (MASLD). This evolution reflects increased understanding of the complex pathophysiology linking local and systemic pathways. The need for an appropriate classification of individual phenotypes has led to the exploration of various pharmacological approaches, including antidiabetic drugs, gut-liver axis agonists, and anti-fibrotic and anti-inflammatory agents. The complex pathophysiology of MASLD makes finding a single effective treatment challenging, but recent advances suggest the potential for personalized therapy. The article also highlights the importance of lifestyle changes, such as diet and physical exercise, in managing MASLD, along with the role of bariatric surgery and targeted pharmacological interventions. The high healthcare burden associated with MASLD underscores the urgent need for new, effective, and safe drugs, as well as accurate characterization of individual phenotypes.The article discusses the growing global burden of liver steatosis associated with metabolic diseases, emphasizing its progression to more severe liver damage and increased risk of cardio-metabolic diseases and cancer. The terminology has evolved from "nonalcoholic fatty liver disease" (NAFLD) to "metabolic dysfunction-associated fatty liver disease" (MAFLD) and finally to "metabolic dysfunction-associated steatotic liver disease" (MASLD). This evolution reflects increased understanding of the complex pathophysiology linking local and systemic pathways. The need for an appropriate classification of individual phenotypes has led to the exploration of various pharmacological approaches, including antidiabetic drugs, gut-liver axis agonists, and anti-fibrotic and anti-inflammatory agents. The complex pathophysiology of MASLD makes finding a single effective treatment challenging, but recent advances suggest the potential for personalized therapy. The article also highlights the importance of lifestyle changes, such as diet and physical exercise, in managing MASLD, along with the role of bariatric surgery and targeted pharmacological interventions. The high healthcare burden associated with MASLD underscores the urgent need for new, effective, and safe drugs, as well as accurate characterization of individual phenotypes.