Lateral flow assays (LFAs) are rapid, inexpensive, easy-to-manufacture and -use tests widely employed in medical and environmental applications, particularly in low resource settings. Historically, LFAs have been stigmatized as having limited sensitivity. However, as their global usage expands, extensive research has demonstrated that it is possible to substantially improve LFA sensitivity without sacrificing their advantages. In this critical review, we have compiled state-of-the-art approaches to LFA sensitivity enhancement. Moreover, we have organized and evaluated these approaches from a system-level perspective, as we have observed that the advantages and disadvantages of each approach have arisen from the integrated and tightly interconnected chemical, physical, and optical properties of LFAs.