Exploration of the ubiquitin system in eukaryotes has shown that the chemical modification of proteins by ubiquitin, known as ubiquitylation, is an incredibly important post-translational event that is crucial to numerous cellular processes. Ubiquitylation is carried out by a series of enzymes that specifically target proteins to either change their activity or their location or earmark them for degradation. Using a wide range of genome-wide approaches, the ubiquitin system has been shown to be of particular importance in the survival and propagation of the human malaria parasites. In this review, we highlight our current understanding of the ubiquitin system in Plasmodium, and discuss its possible role in the development of drug resistant malaria strains.