Wnts are secreted signaling proteins which play decisive roles in developmental processes. Upon deregulation, the canonical Wnt pathway is implicated in the generation of neoplasia. The canonical Wnt signaling initiates by binding of Wnts to the receptor complex consisting of the Frizzled receptor and LRP5/6 coreceptors, members of the low-density lipoprotein receptor family (LDLR). This leads to the stabilization of β-catenin that binds to TCF/LEF transcription factors, resulting in the activation of Wnt target genes. For correct developmental processes the Wnt signaling is constitutively switched off due to the negative regulation exerted by two major multiprotein complexes–the β-catenin degradation complex and the TCF/LEF-transcriptional complex. In addition, the Wnt pathway is also negatively regulated by extracellular antagonists, such as members of the Frizzled Related Proteins (FRP) and Dickkopf (Dkk) families. Here we review our recent data suggesting that HFz6, a member of the Frizzled family and LRP1, a member of the LDLR family, are negative regulators of the Wnt pathway. This negative regulation serves to fine-tune the strict regulation of the Wnt signaling pathway under distinct environmental contexts, which is essential for accurate coordination of various developmental processes.