The short chain fatty acid valproic acid (VPA, 2-propylpetanoic acid) is approved for the treatment of epilepsia, bipolar disorders and migraine and clinically used for schizophrenia. In 1999, the first clinical anti-cancer trial using VPA was initiated. Currently, VPA is examined in numerous clinical trials for different leukaemias and solid tumour entities. In addition to clinical assessment, the experimental examination of VPA as anti-cancer drug is ongoing and many questions remain unanswered. Although other mechanisms may also contribute to VPA-induced anti-cancer effects, inhibition of histone deacetylases appears to play a central role. This review focuses on recent developments regarding the anti-cancer activity of VPA.