Terrestrial plants have developed structural and physiological traits to maintain water balance under variable environments. Protective surfaces reduce water loss but also restrict CO2 diffusion. This constraint has been overcome via stomata, which control gas exchange between plant and atmosphere. Moreover, the development of an efficient xylem allowed long-distance water transport and higher growth. The soil–plant–atmosphere continuum (SPAC) establishes that water fluxes are governed by water potential gradients and are modulated by plant hydraulic traits. The atmosphere is the ultimate driver of water fluxes. It determines the strength of the gradient that sustains transpiration, establishing a strong vapor pressure gradient between the leaf and the surrounding air (i.e., the vapor pressure deficit, VPD). We focus on how high VPD by itself can negatively affect plant functioning. Specifically, we analyze: (i) cuticle as a protective surface to reduce water loss, (ii) stomata as the regulator of gas exchange between plant and atmosphere, (iii) plant water transport at long distances to supply water to transpiring surfaces, and (iv) drought-avoidance strategies reflecting contrasting coordination between stomatal regulation and hydraulic supply. VPD is a central factor shaping plant structure, physiology and survival, revealing the need for a coordinated response at whole-plant level.