The study of blood drop drying has attracted the attention of several research groups for two main reasons:(1) for biomedical purposes as a rapid and cheaper disease detector, and (2) for forensic applications for the interpretation of bloodstain at crime scenes. Also, it presents an interdisciplinary and challenging research subject. However, the mechanisms related to the formation of patterns at the end of the drying process are not fully understood, so this topic still represents an active branch of research that requires further efforts. When a drop of blood is deposited on a non-porous substrate in an unsaturated medium, it spreads and at the same time evaporates. The spreading is described by two regimes, a first regime controlled by the viscous-capillary balance and a second one controlled by the viscous-evaporation balance. The drop spreads until it reaches equilibrium, subsequently it keeps evaporating. The drying process is described by five distinct stages, and the final pattern is divided into three regions: the periphery, the corona, and the central region. The corona region results from the existence of a capillary flow inside the drop that transports the components to the edge of the drop (coffee ring effect). During the drying process, cracks form on the central region and the corona, this is explained in the literature by the competition between evaporation in the gel phase and adhesion to the substrate. These mechanisms (from spreading to final pattern formation) are influenced by the blood composition, the drop size, the substrate nature (wettability and contact angle), the relative humidity, and the temperature. In this chapter, we highlight the significant advances in the drying of human whole blood drops and the influence of these parameters.