The aquatic environment contains many opportunistic pathogens and fish are frequently infected by a range of parasites, bacteria, viruses, and fungi. In most incidences of disease, the involvement of two or more pathogens are often seen, which in turn complicates diagnosis and treatment. Here we present a few case studies on mixed infections in aquaculture systems, which may become more common in future due to changing climatic patterns and associated adverse impacts on water quality. Mixed infections seem to be a big challenge to diagnostic laboratories and health specialists in terms of providing a correct diagnosis and treatment.