Ficus species have adapted to diverse environments and pests by developing physical or chemical protection strategies. Physical defences are based on the accumulation of minerals such as calcium oxalate crystals, amorphous calcium carbonates and silica that lead to tougher plants. Additional cellular structures such as non-glandular trichomes or laticifer cells make the leaves rougher or sticky upon injury. Ficus have also established structures that are able to produce specialized metabolites (alkaloids, terpenoids, and phenolics) or proteins (proteases, protease inhibitors, oxidases, and chitinases) that are toxic to predators. All these defence mechanisms are distributed throughout the plant and can differ depending on the genotype, the stage of development or the environment. In this review, we present an overview of these strategies and discuss how these complementary mechanisms enable effective and flexible adaptation to numerous hostile environments.