Deregulated gene expression including epigenetic modulation is considered one of the most prominent factors that leads to tumorigenesis, thus nominating transcriptional regulators as potential therapeutic targets. Among these epigenetic regulators is a family of evolutionarily conserved motifs known as bromodomains (BRDs), which can be further subcategorized into extraterminal BRDs (BET) or non-BET BRDs. Functionally, BRDs belong to epigenetic readers that bind to acetylated lysine residues on the histone tails and then act as transcriptional coactivators via the recruitment of partner transcriptional factors to the activation sites of target genes. Moreover, BRDs are known for their structural complexity endowed by their varied regulations based on their isoforms, expression pattern, and functionality within diverse tumor types. Provided the prominence of their biological activity and the fact that they get deregulated in different tumor types, growing research efforts are increasingly devoted for developing small molecules targeting them. Intriguingly, BRD inhibitors were reported to suppress the transcription of oncogenes at doses that are well-tolerated by normal tissue, a property that promoted their progress in clinical testing. In this review, we will highlight the structural diversity among the different classes of BET inhibitors along with their molecular targets. Special focus will be lent to BRD4 along with shedding light on the potential attributes leading to therapeutic selectivity of its inhibitors. This collective review paves the way for better understanding of the SAR of BET inhibitors to expectantly expedite advances in development of new inhibitors possessing optimum affinity and selectivity.