Analytical methods are needed to elucidate modern and complex compounds as well as to describe their physical properties. The underlying principles of chalcogen chemistry as well as the natural abundance of chalcogen elements are the base of building many biological substances, including sophisticated materials for future applications. Thus, the need for modern and state-of-the art analytical methods and techniques to characterize them, is obvious. In this chapter, challenges in analytical methods for chalcogen compounds and materials, as well as some examples of natural or synthesized materials or their combinations, including biomaterials, are discussed. Modern methods for chalcogen compounds analysis and structural determination discussed include: UV-Visible and infrared spectroscopy (UV-Vis and IR), thermo analysis, electrochemistry, magnetic analysis, chromatography, X-ray methods (mostly XRF, XRD, and EDX), high-resolution microscopy (SEM and TEM), multinuclear NMR, computational analysis, and bioassay. Also, the historical background and nature of chalcogen elements, including reactivity and magnetic properties as well as thermal behavior, common compounds of chalcogen elements: organic and inorganic materials, complex chalcogen materials, will be briefly discussed.