Epigenetic mechanisms play a fundamental role in normal cellular development and gene expression. Abnormal regulation of epigenetic processes lead to aberrant gene expression, and is a prominent theme in malignant transformation and progression. The plasticity of the epigenome makes it attractive for targeted drug intervention in malignant settings. Novel small molecules directed against members of the BET protein family are a proof of principle of this premise. Based on promising in vitro and in vivo pre-clinical data, clinical trials are currently underway. However, the therapeutic consequences of BET inhibition in this context are yet to be fully elucidated and may be driven by a variety of currently undefined molecular mechanisms and transcriptional programs with differential effect in cellular subsets. The development and optimisation of a methodology to visualise and trace the activity of targeted cancer therapies within a cellular context is an exciting area of current research. The novel approach outlined below aims to use cutting edge chemistry to convert small molecules into molecular probes thus allowing the drugs to be used as investigational tools to characterise their molecular and cellular effects both in vitro and of tracking a therapeutic small molecule in vitro, will lead the way for broader application in vivo. Ultimately this will provide much needed information for the clinical application of BET inhibitors in haematological malignancies, and may be adapted to track other targeted therapies in other pathological settings. The successful elucidation of mechanisms underlying drug action in this manner will not only revolutionise the therapeutic and clinical application of BET inhibitors but has great potential benefit to the broader application and development of all existing and future rationally designed small molecule drugs.