Injuries occur when an athlete performs a greater amount of activity than what their body can withstand. To maximize the positive effects of training while avoiding injuries, athletes and coaches need to determine safe activity levels. The International Olympic Committee has recommended using the acute:chronic workload ratio (ACWR) to monitor injury risk and has provided thresholds to minimize risk when designing training programs. However, there are several limitations to the ACWR and how it has been analyzed which impact the validity of current recommendations and should discourage its use. This review aims to discuss previously published and novel challenges with the ACWR, and strategies to improve current analytical methods. In the first part of this review, we discuss challenges inherent to the ACWR. We explain why using a ratio to represent changes in activity may not always be appropriate. We also show that using exponentially weighted moving averages to calculate the ACWR results in an initial load problem, and discuss their inapplicability to sports where athletes taper their activity. In the second part, we discuss challenges with how the ACWR has been implemented. We cover problems with discretization, sparse data, bias in injured athletes, unmeasured and time-varying confounding, and application to subsequent injuries. In the third part, conditional on well-conceived study design, we discuss alternative causal-inference based analytical strategies that may avoid major flaws in studies on changes in activity and injury occurrence.