Ultrasound guidance has become popular for performance of regional anesthesia and analgesia. This systematic review summarizes existing evidence for superior risk to benefit profiles for ultrasound versus other techniques. Medline was systematically searched for randomized controlled trials (RCTs) comparing ultrasound to another technique, and for large (n > 100) prospective case series describing experience with ultrasound-guided blocks. Fourteen RCTs and 2 case series were identified for peripheral nerve blocks. No RCTs or case series were identified for perineural catheters. Six RCTs and 1 case series were identified for epidural anesthesia. Overall, the RCTs and case series reported that use of ultrasound significantly reduced time or number of attempts to perform blocks and in some cases significantly improved the quality of sensory block. The included studies reported high incidence of efficacy of blocks with ultrasound (95%-100%) that was not significantly different than most other techniques. No serious complications were reported in included studies. Current evidence does not suggest that use of ultrasound improves success of regional anesthesia versus most other techniques. However, ultrasound was not inferior for efficacy, did not increase risk, and offers other potential patient-oriented benefits. All RCTs are rather small, thus completion of large RCTs and case series are encouraged to confirm findings.