The development of biomaterials for specific application with the desired function requires a careful combination of surface roughness, surface energy (and their polar and dispersion component), the presence of functional group, and the response of materials to the body fluid. The main constituent of body fluid is water; therefore, material response to water can be used to predict the behavior of the material implanted in the human body. Protein adsorption, cell and bacteria proliferation, alkaline phosphate activity, and so on are some of the assessments that are conducted during the in vitro studies on the materials, which depend on the hydrophilic or hydrophobic nature of the material in order to provide first insight into the material response. These responses of the material further depend on surface roughness, surface energy and the presence of functional group on the surface. Hence, learning the wetting behavior of material is necessary for its engineering. Thus, to nurture the material behavior in the body environment, understanding of contact angle (CA), its dependence on various factors and fabrication of desired surface is extremely necessary. In this chapter, the basics of CA in contrast to natural phenomena present in the surrounding environment such as surfaces of lotus, rice and ramie leaves, correlations between the morphological