NMR provides powerful structural elucidation tools that are particularly well suited for natural products studies. Comprehensive spectroscopic characterization of a native metabolite may be sufficient to fully assign a planar structure. However assignment of the relative and absolute configuration of a molecule when there are multiple stereogenic centers often requires the development and application of additional experimental strategies. Many successful approaches in this regard rely on the formation of appropriate derivatives for more detailed NMR study. Since natural products are often obtained in very limited quantities, micro-scale chemical manipulations and the ability to analyze the structure of the resulting products is often key to the complete structural and configurational assignment of complex metabolites. Anisotropic NMR parameters such as residual dipolar coupling (RDC) and residual chemical shift anisotropy (RCSA) provide a powerful and complementary means to help assign and verify structures deduced from conventional NMR analyses. Application of a wide spectrum of NMR techniques and methodologies will be described in the structural elucidation of two novel alkaloid scaffolds and a new phosphomacrolide marine natural product with 8 stereogenic centers.