Lipodystrophy is an acquired or inherited disorder of fat metabolism that may be clinically evident as lipohypertrophy, lipoatrophy and metabolic abnormalities. The pathogenesis of lipodystrophy is likely multifactorial, involving effects of antiretroviral medications, HIV itself, genetic factors, host factors and still more remains to be established. The laboratory technique involves Anthropometry, MRI, DXA, CT and Ultrasonography is helpful to assess fat content at regular timings. It is categorized into acquired and inherited forms, associated with complications of diabetes mellitus, dyslipidemia and other metabolic abnormalities. The proper usage of diet, exercise, nutrition, anti-diabetic drugs, hyper-lipidemic drugs, alterations in HIV medication are useful for regulating the lipodystrophy upto an extent. The usage of leptin and adiponectin increases their circulating levels of PPAR-γ agonists, for therapeutic purposes. Other novel approaches, include GH, GHRF, laser, stem cell therapy and other potential surgical applications guides to therapeutic armamentarium. New insights from research and clinical trials could potentially revolutionize the lipodystrophy management.