In living organisms, cells sense mechanical forces (shearing, tensile, and compressive) and respond to those physical cues through a process called mechanotransduction. This process includes the simultaneous activation of biochemical signaling pathways. Recent studies mostly on human cells revealed that compressive forces selectively modulate a wide range of cell behavior, both in compressed and in neighboring less compressed cells. Besides participating in tissue homeostasis such as bone healing, compression is also involved in pathologies, including intervertebral disc degeneration or solid cancers. In this review, we will summarize the current scattered knowledge of compression-induced cell signaling pathways and their subsequent cellular outputs, both in physiological and pathological conditions, such as solid cancers.