Long noncoding RNAs (lncRNAs) are large RNA transcripts that do not code for proteins but exert their effects in the form of RNA. To date many thousands of lncRNAs have been identified, their molecular functions and mechanisms of action however are largely unknown. The development of high-throughput experimental technologies, such as ChIRP (Chromatin isolation by RNA purification), CHART (Capture Hybridization Analysis of RNA Targets), RAP (RNA antisense purification), RIP (RNA Immunoprecipitation), CLIP (cross-linking and immunoprecipitation) and RNA pull-down, has led to a rapid expansion of lncRNA research and resulted in many publicly-available databases. This review provides an overview of the current methodologies available for discovering and investigating functions of lncRNAs in various human diseases. A comparison and application of these methods are also included. Finally, this paper surveys current databases containing annotations, interactome networks and functions of lncRNAs. The appropriate use of these methods and databases will provide not only high-resolution functional features of lncRNAs, but also enhance our understanding of the underlying mechanisms by which lncRNAs regulate a variety of biological processes.