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Treatment of bone and joint infections can be challenging as antibiotics should penetrate through the rigid bone structure and into the synovial space. Several pharmacokinetic studies measured the extent of penetration of different antibiotics into bone and joint tissues. This review discusses the results of these studies and compares them with minimum inhibitory concentrations (MIC) of common pathogens implicated in bone and joint infections in order to determine which antibiotics may have a greater potential in the treatment of such infections. Clinical outcomes were also evaluated as data were available. More than 30 antibiotics were evaluated. Overall, most antibiotics, including amoxicillin, piperacillin/tazobactam, cloxacillin, cephalosporins, carbapenems, aztreonam, aminoglycosides, fluoroquinolones, doxycycline, vancomycin, linezolid, daptomycin, clindamycin, trimethoprim/sulfamethoxazole, fosfomycin, rifampin, dalbavancin, and oritavancin, showed good penetration into bone and joint tissues reaching concentrations exceeding the MIC 90 and/or MIC breakpoints of common bone and joint infections pathogens. Few exceptions include penicillin and metronidazole which showed a lower than optimum penetration into bones, and the latter as well as flucloxacillin had poor profiles in terms of joint space penetration. Of note, studies on joint space penetration were fewer than studies on bone tissue penetration. Although clinical studies in osteomyelitis and septic arthritis are not available for all of the evaluated antibiotics, these pharmacokinetic results indicate that agents with good penetration profiles would have a potential utilization in such infections.