The Chilean Gracilaria chilensis (now named Agarophyton chilense), has been cultivated in Chile since 1980, after the collapse of natural populations due to overharvesting. Cultivation is extensive, dominated by small-scale, artisanal farms. Cultivation is achieved by clonal propagation, after replanting part of the harvested biomass. This practice, together with over-harvesting, led to a strong genetic erosion, and most farms are dominated by one or very few clones. Since 2000, biomass production is decaying in Chile, a trend attributed to the loss of biomass quality (i.e., reduced growth rates and epiphytic load). Epiphytes are highly diverse in terms of species composition and the impacts they cause to the host. We proposed a classification of these impact and show that many are causing observable diseases to their host. Besides the low genetic diversity, it is possible to detect resistant strains in farms. This resistance is expressed by the reduction of germination rates and development of epiphytes on Gracilaria’s surface. It is associated with the activation of metabolic pathways triggered by the hydroxylation of fatty acids, and the resistance can be induced by the use of these molecules. We are now exploring the genomic regulation of these pathways and the role of genetic diversity in modulating the spread of epiphytes withing farms. We also investigate how cultivation practices drive the domestication of G. chilensis, and what strategies could provide better resilience to environmental variability and epiphytism.