Female athletes are at a 4- to 6-fold increased risk of anterior cruciate ligament (ACL) injury compared with male athletes. There are several medical, emotional and financial burdens associated with these injuries. Sex hormones may be involved in the ACL injury disparity, with potential associations reported between phases of the menstrual cycle and ACL injury rates. The reported relationships between ACL injury and menstrual status may be related to associated changes in ligament mechanical properties from cyclic fluctuations of female sex hormones. A PubMed electronic database literature search, including MEDLINE (1966-2005) and CINAHL (1982-2005), with the search terms 'menstrual cycle' and 'knee laxity' was used for this systematic review. Studies were included in this systematic review if they were prospective cohort studies and investigated the association between the menstrual cycle and anterior knee laxity in females. Nine prospective cohort studies, published as 11 articles, were included in the systematic review. Six of nine studies reported no significant effect of the menstrual cycle on anterior knee laxity in women. Three studies observed significant associations between the menstrual cycle and anterior knee laxity. These studies all reported the finding that laxity increased during the ovulatory or post-ovulatory phases of the cycle. A meta-analysis, which included data from all nine reviewed studies, corroborated this significant effect of cycle phase on knee laxity (F-value = 56.59, p = 0.0001). In the analyses, the knee laxity data measured at 10-14 days was >15-28 days which was >1-9 days. Future studies testing the relationship between the menstrual cycle and potentially associated parameters should consider the limitations outlined in this article and control for potential biases and confounders. Power analyses should be utilised. Subjects should be randomly entered into the studies at alternate points in the cycle, and standard and consistent data acquisition and reporting methods should be utilised. Future studies should clearly define what constitutes a 'normal' cycle and appropriate control subjects should be utilised. Furthermore, there is a need to define cycle phase (and timing within cycle phase) with actual hormone levels rather than a day of the cycle. Although hormone confirmations were provided in many of the studies that selected specific days to depict a particular cycle for all women, it is unknown from these data if they truly captured times of peak hormone values in all women. A combined systematic review and meta-analysis of the literature indicate that the menstrual cycle may have an effect on anterior-posterior laxity of the knee; however, further investigation is needed to confirm or reject this hypothesis.