A synopsis of the lichen family Gomphillaceae in eastern North America is presented, based mainly on collections made by the second author during the past 30 years. A total of 57 taxa is reported for the area, including 11 species and one variety new to science: Arthotheliopsis floridensis Lücking & W. R. Buck, sp. nov., Echinoplaca areolata Lücking & W. R. Buck, sp. nov., Gyalectidium tuckerae Lücking & Lendemer, sp. nov., G. viride Lücking, W. R. Buck & Rivas Plata, sp. nov., Gyalideopsis americana Lücking & W. R. Buck, sp. nov., G. ozarkensis Lücking, W. R. Buck & R. C. Harris, sp. nov., G. subaequatoriana Lücking & W. R. Buck, sp. nov., G. submonospora Lücking & W. R. Buck, sp. nov., G. vainioi var. semicirculata Lücking & W. R. Buck, var. nov., Tricharia floridensis Lücking & W. R. Buck, sp. nov., T. subumbrosa Lücking & W. R. Buck, sp. nov., and T. tuckerae Lücking & W. R. Buck, sp. nov. The new combinations Gyalideopsis berenice (Ellis & Everh.) Lücking & W. R. Buck, comb. nov. (Basionym: Stilbomyces berenice Ellis & Everh.) and G. epicorticis (A. Funk) Tønsberg & Vězda, comb. nov. (Basionym: Microlychnus epicorticis A. Funk) are made. In addition, the following taxa are added to the checklist of North American lichens: Arthotheliopsis planicarpa (Lücking) Lücking, Sérus. & Vězda, Calenia solorinoides Lücking, Echinoplaca furcata subsp. neotropica Lücking, E. lucernifera Kalb & Vězda, E. similis Kalb & Vězda, E. tetrapla (Zahlbr.) Lücking, Gyalectidium catenulatum (Cavalc. & A. A. Silva) L. I. Ferraro, Lücking & Sérus., Gyalideopsis africana Kalb & Vězda, G. aff. argentea (Mont.) Kalb & Vězda, G. lambinonii Vězda, G. macarthurii Lücking, Umaña & Aptroot, G. wesselsii Lücking, Sipman & Chaves, Tricharia cuneata L. I. Ferraro & Vězda, T. aff. farinosa R. Sant. and T. vainioi R. Sant. Keys and selected distribution maps are presented. Rich material of Gomphillus americanus Essl., Gyalideopsis berenice and G. buckii Lücking, Sérus. & Vězda (≡ Tricharia vezdae W. R. Buck) allowed for a detailed study on hyphophore development in these species.