To reduce attrition rates in pharmaceutical research and development (R&D), powerful quantitative analytical methods are needed to monitor therapeutic compounds, their metabolites, and target engagement. The ability of matrix-assisted laser desorption/ ionisation (MALDI) imaging to perform quantitative spatial analysis of drugs and their metabolites, as well as pharmacodynamic (PD) biomarkers in tissues, is accelerating its use in pharmaceutical research. Dale Shannon Cornett at Bruker describes how advances in technology and methodology are opening MALDI imaging up to analysing a wider range of small molecules without compromising image resolution.