Currently, an increasing number of receptors appear to belong to the dependence receptors family. These proteins have the capacity to induce a program of apoptosis in settings of absence of their ligand. A cell that expresses one of these receptors is thus dependent on the presence of the ligand to survive. The observation that these receptors are lost in many cancers is then suggesting that this loss is a selective advantage for tumor development because it leads tumor cells not to be dependent for survival on the presence of the ligand. We propose to focus this review on the role of some of these receptors that have been intensively studied: the dependence receptors that bind the netrin-1. After having pointed out their role in the development of the nervous system and in cell death induction, we will discuss their putative role in the pathological context of tumorigenesis and more particularly in the control of colorectal cancers.