We undertook a systematic review of the literature concerning the efficacy and safety of bisphosphonates in acute Charcot neuropathic osteoarthropathy. MEDLINE, PubMed, the Cochrane Database of Systematic Reviews, and abstracts presented during the meetings of the American Diabetes Association and the European Association of Diabetes were searched for relevant publications from the period January 1990 to September 2011. A total of ten studies on the treatment of acute Charcot osteoarthropathy with bisphosphonates were identified and included in the analysis. Only four clinical trials were published, three of which were randomised. Bisphosphonates appeared to induce significant reductions in skin temperature and bone turnover markers compared with placebo, without serious adverse events. Nevertheless, bisphosphonates did not shorten the immobilisation time. Moreover, no data were available regarding their long-term effects. Bisphosphonates have been shown to be effective for reducing bone turnover markers and skin temperature in some studies. Nevertheless, the long-term efficacy, specifically that regarding the occurrence of deformities and ulcerations, remains to be demonstrated as no follow-up studies have been published. Moreover, some studies have suggested that bisphosphonates may lengthen the resolution phase of the disease. In our opinion, the data are too weak to support the use of bisphosphonates as a routine treatment for acute Charcot neuroarthropathy.