Complex regional pain syndrome (CRPS) can result in a devastating condition. For a small number of patients, there is a non-response to any existing multimodal therapies and they ultimately request amputation. Such a drastic and final decision is not easy to take for both the patient and the surgeon and requires careful and interdisciplinary assessments and considerations. Furthermore, new surgical procedures, such as targeted muscle reinnervation (TMR) and hybrid prosthetic fitting, and multidisciplinary board advice should be included when considering amputation. In order to help other therapeutic teams in decision making for such rare but more than demanding cases, we aimed to propose an advanced algorithm for amputation indications in CRPS patients combining all these new factors. This algorithm consists of extensive pre-operative psychiatric assessment, diagnostic hybrid prosthetic fitting including fMRI analyses, multidisciplinary board advice as well as targeted muscle reinnervation and amputation procedures with final prosthetic fitting and rehabilitation. By involving multiple disciplines, this algorithm should provide optimized and individualized patient treatment on the one hand and a reliable base for decision making for therapists on the other.