It is known that chemotherapy induces alopecia in humans, with important psychological and social implications in spite of its reversibility. Among chemotherapeutic drugs, anthracyclines are widely used, yet cause severe alopecia. One of the causes for the elevated sensibility of hair follicles to anthracyclines, and to drugs in general, is the high proliferation rate of follicular epithelium and the long duration of the growth phase (up to 7 years in humans). To clarify the mechanism of anthracycline toxicity, we used a rat model and focused our attention on the morphological alterations in hair follicles induced by doxorubicin. We observed the progression of hair follicle degeneration in the epithelial and mesenchymal compartments until alopecia arose, by both light and electron microscopy. As a first sign of damage, significant apoptosis was detected in the proximal perifollicular connective tissue sheath and sporadically in the matrix, near the interface between matrix and follicular papilla. We propose the apoptotic remodeling of the mesenchymal compartment as a process that is fundamental to the progression of events leading to alopecia. Regarding the epithelial compartment, it is important to note that oncosis was observed in a large number of follicular cells in the outer root sheath during the last stages of hair follicle regression. This indicates that oncosis is involved in a major way in the damage of epithelial cells.