Imaging mass spectrometry (IMS) encompasses a variety of techniques that enable the chemical imaging of analytes, which range in size from atoms and small molecules to intact proteins, directly from biological tissues. IMS is transforming specific areas in biological research with its unique combination of chemical and spatial information. Innovations in instrumentation and imaging protocols will make this approach invaluable at many stages of the drug discovery process, including pharmacological target screening and evaluating the distribution of drug and drug metabolites in cells and tissues. The fundamentals and unique methodology of IMS are discussed, along with exciting new applications to drug discovery science. The promise of imaging mass spectrometry: the direct measurement of the molecular and spatial distribution of hundreds of compounds from a biological tissue. Are we there yet?