Mitochondria are the “power generators” in eukaryotic cells, therefore playing vital roles for basically all cellular activities. Not only supplying energy, mitochondria are also actively regulating important cellular processes, such as apoptosis, differentiation, and proliferation. But mitochondria are not “perpetual motion machines”. In fact, mitochondria are one of the most sensitive organelles to various pathological conditions. Dysfunction of mitochondria can cause many human diseases, such as Alzheimer's disease, diabetes, ischemic heart disease, etc. It is well known that changes in mitochondrial morphology affect the mitochondrial function, and vice versa. Under pathological conditions, mitochondria undergo various morphological changes. Research studies that characterized abnormal mitochondrial morphology have enabled us to understand the mitochondrial involvement in the pathogenesis of certain human diseases. This review mainly summarizes the research progress on mitochondrial morphological changes in human diseases, aiming to provide a theoretical overview.