Palladium catalysed reactions are ubiquitous in synthetic organic chemistry in both organic solvents and aqueous buffers. The broad reactivity of palladium catalysis has drawn interest as a means to conduct orthogonal transformations in biological settings. Successful examples have been shown for protein modification, in vivo drug decaging and as palladium-protein biohybrid catalysts for selective catalysis. Biological media represents a challenging environment for palladium chemistry due to the presence of a multitude of chelators, catalyst poisons and a requirement for milder reaction conditions e.g. lower temperatures. This review looks to identify successful examples of palladium-catalysed reactions in the presence of proteins or cells and analyse solutions to help to overcome the challenges of working in biological systems.