Regional anesthesia has shown to be successful in controlling major pain in trauma patients. However, the possibility of masking acute compartment syndrome (ACS) after peripheral nerve blocks for limb injuries is still controversially discussed. Therefore, we aimed to summarize the current literature regarding this topic to shed light on the impact of peripheral regional anesthesia on the diagnosis of ACS in trauma patients. We searched Pubmed, Google Scholar and the Cochrane Library for literature following the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. The analysis of these reports was included in the context of the current literature concerning this topic. We found no (randomized) studies, and only six case reports dealing with the impact of peripheral nerve blocks and ACS in patients after a limb trauma met our criteria and were included in our review. Only one reported a delay in the diagnosis of ACS. In most of the cases (5 of 6), the breakthrough pain, despite the nerve block, proved to be a good indicator of a developing ACS. However, despite some narrative articles about the topic including some recommendations about the possibly safe use of regional anesthesia techniques for limb trauma, there is still no international consensus and only one national guideline focusing on the possibly safe use of peripheral nerve blocks in trauma patients at risk of ACS. After reviewing the respective literature, we consider that intra-articular analgesia, sensory blocks, fascial plane blocks and low-concentration continuous peripheral nerve blocks are effective for analgesia and a low-risk analgesia tool for trauma and postsurgical patients at risk of ACS due to the fact that they do not lead to a dense block. Finally, we summarized suggestions based on the results of the literature for the different regional anesthesia modalities in these patients in a table to facilitate the use of these techniques.