Introduction. Pyoderma gangrenosum (PG) is a neutrophilic dermatosis often associated with autoimmune disease that, despite published literature, still poses diagnostic and therapeutic challenges due to its lack of serological and histological markers and wide possibility of differential diagnosis. Although immunosuppressive therapy usually is the first-line treatment, it has a long-lasting, unpredictable treatment course, thus necessitating the need for new treatment options. This report highlights 2 cases of PG ulcers treated with different methods that show a potentially faster healing time, as well as a review of advanced treatment options for PG. Case Reports. Two men (21 years old and 64 years old) presented with PG ulcers and underwent 2 different treatment courses. The 21-year-old man received negative pressure wound therapy (NPWT) with a nonadhesive, less-invasive, skin-contact interface layer on the polyurethane foam. Stimulated growth of granulation tissue accelerated healing and prepared the wound bed for further epithelization. The second patient, the 64-year-old man, underwent treatment with autologous platelet-rich fibrin, which supplied the ulcer with growth factors and accelerated epithelialization. Conclusions. The new possibilities offered by NPWT with nonadhesive foam and regenerative medicine are typically affordable, effective, safe, and painless for the patient. Both methods were noninvasive, did not accelerated the pathergy phenomenon, and showed a potential for faster healing of PG ulcers.