Long COVID, a post-acute sequelae of SARS-CoV-2 infection, is a newly recognized chronic condition causing disability in some individuals. Despite significant progress in understanding its epidemiology, biology, and pathophysiology, there is no cure for the tens of millions affected. The review highlights the need for sustained investment in research and development to address long COVID and other infection-associated chronic conditions. Long COVID is defined as a chronic disease state with symptoms lasting at least 3 months, including unexplained symptoms, new or worsened medical conditions, and post-hospitalization syndromes. The condition is highly heterogeneous, and its mechanisms are complex, involving biological and physiological processes that may overlap. The review discusses the role of SARS-CoV-2 infection in causing long-term health issues, including post-acute inflammation, immune dysfunction, and autoimmunity. It also explores the potential of antiviral therapies, immunomodulators, and anti-inflammatory treatments in preventing and treating long COVID. The review emphasizes the importance of defining long COVID clearly and developing targeted therapies based on its underlying mechanisms. The role of persistent viral replication, chronic inflammation, and immune dysfunction in long COVID is discussed, along with the potential of therapies targeting these processes. The review concludes that a comprehensive approach is needed to address long COVID, including research into its mechanisms, development of biomarkers, and clinical trials to test potential treatments.Long COVID, a post-acute sequelae of SARS-CoV-2 infection, is a newly recognized chronic condition causing disability in some individuals. Despite significant progress in understanding its epidemiology, biology, and pathophysiology, there is no cure for the tens of millions affected. The review highlights the need for sustained investment in research and development to address long COVID and other infection-associated chronic conditions. Long COVID is defined as a chronic disease state with symptoms lasting at least 3 months, including unexplained symptoms, new or worsened medical conditions, and post-hospitalization syndromes. The condition is highly heterogeneous, and its mechanisms are complex, involving biological and physiological processes that may overlap. The review discusses the role of SARS-CoV-2 infection in causing long-term health issues, including post-acute inflammation, immune dysfunction, and autoimmunity. It also explores the potential of antiviral therapies, immunomodulators, and anti-inflammatory treatments in preventing and treating long COVID. The review emphasizes the importance of defining long COVID clearly and developing targeted therapies based on its underlying mechanisms. The role of persistent viral replication, chronic inflammation, and immune dysfunction in long COVID is discussed, along with the potential of therapies targeting these processes. The review concludes that a comprehensive approach is needed to address long COVID, including research into its mechanisms, development of biomarkers, and clinical trials to test potential treatments.