Lysosomes are conserved organelles that are present in all eukaryotic cells. They are part of a complicated network of intracellular trafficking routes - the lysosomal transport system. Lysosomes are necessary for the maintenance of cellular homeostasis and for many specialized functions, including the activity of many components of the mammalian immune system. Dysfunctions of the lysosomal system are associated with numerous diseases, such as storage disorders, neuro- and myopathies, cancer and some types of albinism and immunological deficiencies. High conservation of the processes of lysosomal biogenesis and transport enables the use of yeast as a model for studying the mechanisms that underlie these diseases. In this review, we discuss several examples of such models in an attempt to present an overview of the most important experimental methods available in yeast research.