Long noncoding RNAs (lncRNAs) are a class of RNA molecules exceeding 200 nucleotides in length that lack long open-reading frames. Transcribed predominantly by RNA polymerase II (>500nt), lncRNAs can undergo splicing and are produced from various regions of the genome, including intergenic regions, introns, and in antisense orientation to protein-coding genes. Aberrations in lncRNA expression or function have been associated with a wide variety of diseases, including cancer, cardiovascular diseases, diabetes, and neurodegeneration. Despite the growing recognition of select lncRNAs as key players in cellular processes and diseases, several challenges obscure a comprehensive understanding of their functional landscape. Recent technological innovations, such as in sequencing, affinity-based techniques, imaging, and RNA perturbation, have advanced functional characterization and mechanistic understanding of disease-associated lncRNAs.