The ‘language’ of covalent histone modifications translates environmental and cellular cues into gene expression. This vast array of post-translational modifications on histones are more than just covalent moieties added onto a protein, as they also form a platform on which crucial cellular signals are relayed. The reversible lysine acetylation has emerged as an important post-translational modification of both histone and non-histone proteins, dictating numerous epigenetic programs within a cell. Thus, understanding the complex biology of lysine acetylation and its regulators is essential for the development of epigenetic therapeutics. In this review, we will attempt to address the complexities of lysine acetylation in the context of tumorigenesis, their role in cancer progression and emphasize on the modalities developed to target lysine acetyltransferases towards cancer treatment.