Background: TGF-β has been identified as a key factor in the progression of various diseases, in particular cancer and fibrosis. The signaling of TGF-β can be modulated through three distinct strategies: using antisense nucleotides that block TGF-β mRNA (trabedersen (AP 12009)), using monoclonal antibodies to block TGF-β isoforms (lerdelimumab, metelimumab) or using small molecule inhibitors of the TGF-β receptor 1 (TGF-βR1 or ALK-5). Objective: This review focuses on small molecules and summarizes the most recent TGF-βR1 inhibitors reported in the patent literature. Methods: We searched and analyzed the patent literature claiming chemical matter for TGF-βR1 inhibition from the 1^st of January 2005 to the 1^st of January 2009. Results/conclusions: The inhibition of TGF-β has recently been clinically validated with antisense nucleotide trabedersen. Small molecules inhibitors of TGF-βR1 that are now in Phase I clinical trials and in preclinical stage are, therefore, of high interest and could provide a more versatile route to TGF-β modulation through oral dosing while maintaining the same therapeutic benefits.