Reversible phosphorylation regulates many aspects of protein function and properties, such as proper folding, localization, binding potential, enzymatic activity, or stability. This chapter focuses on the Plasmodium kinome and on the biology of protein phosphorylation in Plasmodium. It discusses the potential and initial progress in antimalarial drug discovery based on the inhibition of the protein kinases of both the parasite and its host erythrocyte. Methods to manipulate the Plasmodium genome have been developed only relatively recently. The most commonly used methods rely on the transfection of asexual erythrocytic stages of the life cycle, in which the parasite is haploid and replicates continuously, facilitating genetic manipulation and selection of recombinants. The rapid expansion of mass spectrometry‐based proteomic techniques has provided a method of producing a snapshot of the global phosphorylation status of organisms such as yeast and bacteria, as well as cultured eukaryotic cells, and tissues such as the liver.