A summary of the present knowledge on the biogeography and ecology of the known theraphosid spiders in the Darién region, Panama is presented. Hapalopus coloratus (Valerio, 1982) is redescribed, Holothele longipes (L. Koch, 1875), Neischnocolus panamanus (Petrunkevitch, 1925) and Psalmopoeus pulcher Pretunkevitch, 1925 are briefly discussed. Five new species of theraphosid spider are described from the Darién region: Cyclosternum darienensis sp. nov., Euthycaelus quinteroi sp. nov., Pamphobeteus sucreorum sp. nov., Spinosatibiapalpus cambrai sp. nov. and Tapinauchenius herrerai sp. nov. The supposed distribution of the taxa Pamphobeteus ornatus Pocock, 1903 and Xenesthis immanis (Ausserer, 1875) in Panama are rejected. The synonymy of Xenesthis colombiana Simon, 1891 with X. immanis is rejected based on incompatible leg morphometrics and no textual justification thereby restoring X. colombiana comb. rest.