Fibroblasts are a heterogenic cell-type that play a major role in tissue integrity and wound healing. Under pathological conditions they transform into an aggressive phenotype, being responsible for inducing organ fibrosis as well as supporting tumor progression. Fibroblasts are known to secrete abundant amounts of extracellular matrix and numerous growth factors and cytokines. Cell-specific therapeutic targeting to fibroblasts is of high interest for intervening into several pathologies by developing novel therapeutic modalities. This chapter will shed light on the biology of fibroblasts, their diversity and heterogeneity as well as the targeting strategies using different targeting systems, such as nanoparticles and biologicals.