Background and Objectives: Treating segmental tibial and ankle bone loss after radical surgery for chronic osteomyelitis is one of the most challenging problems encountered by orthopaedic surgeons. Open tibia and ankle fractures occur with an incidence of 3.4 per 100,000 and 1.6 per 100,000, respectively, and there is a high propensity of developing fracture-related infection with associated chronic osteomyelitis in patients. Segmental tibial and ankle bone loss have recently received new and improved treatments. Materials and Methods: Above all, 3D printing allows for the customization of implants based on the anatomy of each patient, using a personalized process through the layer-by-layer deposition of materials. Results: This article presents different cases from the authors’ experience. Specifically, four patients suffered tibia and ankle fractures and after radical surgery for chronic osteomyelitis combined with high-performance antibiotic therapy underwent ankle reconstruction/arthrodesis with custom-made tibial spacers. Conclusions: Thanks to 3D-printed patient-specific devices, it is possible to perform surgical procedures that, for anatomical reasons, would have been impossible otherwise. Moreover, an improvement in overall functionality and an important reduction in pain were shown in the last follow-up in all patients.