Accumulating data from large-scale transcriptome studies have identified a class of poorly understood non-protein-coding RNAs, including microRNAs, piwi-interacting RNAs (piRNAs), and long non-coding RNAs (lncRNAs), and a number of studies suggest that lncRNAs modulate the expression of protein-coding genes in a variety of tissues and organs by altering chromatin modification, transcription, mRNA decay, protein subcellular localization, and other key processes. Although much work still remains to identify the roles of lncRNAs in reproduction-related systems, they are likely to exert widespread effects during these processes. In this review, we highlight our emerging understanding of how lncRNAs regulate gene expression, and we discuss the physiological role of this new class of molecular regulators in neurobiology, cardiology, endocrinology, metabolism, muscle biology, and female reproductive disorders.