As many as 60% of investigational new drugs fail in the later preclinical and clinical phases of development because of unsatisfactory absorption, distribution, metabolism, excretion and/or toxicity (ADMET) characteristics. There is therefore a great need for tools that can help to predict the ADMET response earlier in drug development, before valuable resources are wasted on compounds destined ultimately to fail. ADMET characteristics are reliant on many co-ordinated events and feedback pathways in the intact organism and cannot readily be measured accurately in in vitro biochemical assays. The cell, however, as the smallest intact functional unit of living organisms, can provide a useful model in which to carry out predictive ADMET studies. This article looks at automated microscopy and imaging as a useful screening tool in early-stage drug discovery.