The interruption of any stage of the viral life cycle can become an important therapeutic approach for treating CoV‐related diseases. A recent SARS‐CoV‐2‐human protein‐protein interaction analysis showed that SARS‐CoV‐2 contains approximately 66 druggable proteins, each of which has several ligand binding sites. 25  The most interesting coronavirus proteins are the S glycoprotein, proteases Mpro and PLpro, RdRP, and helicase. In this review, we highlight these targets with potential therapeutic development against the highly dangerous pathogens SARS‐CoV‐1 and 2, and MERS‐CoV. Medicinal chemistry efforts toward the evolution of molecules with drug‐like properties is additionally discussed. In addition, broad‐spectrum antivirals targeting the major viruses are reviewed in detail, since they represent a highly promising strategy for treating these often fatal respiratory illnesses.