As there is limited information on the mechanisms of vegetative desiccation tolerance in pteridophytes, we undertook a comprehensive anatomical, ultrastructural, physiological and biochemical study on the fern Mohria caffrorum. Our data show that this species is desiccation-tolerant during the dry season, and desiccation-sensitive in the rainy season. This system allows the verification of protection mechanisms by comparison of tolerant and sensitive tissues of the same species at the same developmental age. Tolerant fronds acquire protection mechanisms during drying that are mostly similar to those reported for angiosperms. These include: (i) chlorophyll masking by abaxial scales and frond curling; (ii) increased antioxidant capacity that is maintained in dry tissues; (iii) mechanical stabilization of vacuoles in the dry state; (iv) de novo production of heat stable proteins (at least one identified as a putative chaperonin); (v) accumulation of protective carbohydrates (sucrose, raffinose family oligosaccharides and cyclitols). This study has implications for the biotechnological production of drought-tolerant crops, and allows speculation on the evolution of vegetative desiccation tolerance.