Non-alcoholic fatty liver disease (NAFLD) has become one of the most prominent 
forms of chronic liver disease worldwide, reflecting the epidemic of global 
obesity. Those with the progressive variant of NAFLD, non-alcoholic 
steatohepatitis (NASH), are at significantly increased risk of multisystem 
morbidity and mortality. However, there are currently no approved pharmacologic 
therapies for NASH. Given the disease burden, there is an important unmet need 
for pharmacologic treatment options for this patient population. The underlying 
pathophysiologic mechanisms that contribute to the development and progression 
of NAFLD and NASH are complex and reflected by the myriad of therapies, with 
different targets, currently under investigation. In broad strokes, drug 
development has focused on modulation of metabolic pathways, inflammatory 
cascades, and/or mechanisms impacting fibrosis. Although much progress has been 
made in enhancing our understanding of NAFLD pathogenesis, development of 
pharmacologic treatments has been hindered by challenges in clinical trial 
enrollment and complexities in clinical trial design. The compounds in phase IIa 
have provided promising results in terms of potential benefits on various 
aspects of histopathology. Agents in later stages of development have shown 
fairly modest results in terms of reduction of hepatic steatosis, 
necroinflammation and fibrosis. If longer term safety and efficacy are 
established among heterogeneous cohorts, these medications may help mitigate 
potential morbidity and mortality for this burgeoning patient population.