Fibrillins are one of the major components of supramolecular fibrous structures in the extracellular matrix of elastic and nonelastic tissues, termed microfibrils. Microfibrils provide tensile strength in nonelastic tissues and scaffolds for the assembly of tropoelastin in elastic tissues, and act a regulator of growth factor bioavailability and activity in connective tissues. Mutations in fibrillins lead to a variety of connective tissue disorders including Marfan syndrome, stiff skin syndrome, dominant Weill-Marchesani syndrome, and others. Therefore, fibrillins are frequently studied to understand the pathophysiology of these diseases and to identify effective treatment strategies. Extraction of endogenous microfibrils from cells and tissues can aid in obtaining structural insights of microfibrils. Recombinant production of fibrillins is an important tool which can be utilized to study the properties of normal fibrillins and the consequences of disease causing mutations. Other means of studying the role of fibrillins in the context of various physiological settings is by knocking down the mRNA expression and analyzing its downstream consequences. It is also important to study the interactome of fibrillins by protein-protein interactions, which can be derailed in pathological situations. Interacting proteins can affect the assembly of fibrillins in cells and tissues or can affect the levels of growth factors in the matrix. This chapter describes important techniques in the field that facilitate answering relevant questions of fibrillin biology and pathophysiology.