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Non-alcoholic fatty liver disease (NAFLD) is the most important cause of chronic liver disease and is considered the hepatic manifestation of the metabolic syndrome associated with obesity and diabetes type 2. NAFLD refers to a wide spectrum of liver damage, including simple steatosis and inflammation, fibrosis, and cirrhosis (non-alcoholic steatohepatitis). The mechanisms involved in NAFLD are multifactorial, insulin resistance being a common factor in the retention of fatty acids and triacylglycerides within hepatocytes with mitochondrial production of free radicals, which trigger oxidative stress, cytokine production, and necrosis. Concomitantly, reduced availability of long chain n-3 polyunsaturated fatty acids is attained, a condition that alter the function of several transcription factors involved in lipolytic and lipogenic processes in the liver. A greater knowledge of the etiopathogenic mechanisms of NAFLD is crucial for the development of future effective therapeutic strategies.