Model organisms have long served for research on fundamental aspects of basic biology. More recently, they have also proven helpful in modeling human diseases, in the identification of drug targets, and in the evaluation of potential therapeutic agents. In this context, this course provides an overview on the most commonly used model organisms (ranging from simple eukaryotes such us budding yeast to more complex ones including nematodes, flies, zebrafish, and mice) and models systems (such as human cell cultures and organoids). We will discuss the specific advantages and limitation of each of these organisms and systems for modeling human diseases including neurodegenerative, cardiovascular, respiratory, muscular, skin, and hyperproliferative diseases including cancer. In addition, we will also delineate how these model systems can be exploited to identify molecular mechanisms and therapeutic strategies for the treatment of diverse human diseases.