The innate immune system consists of a cellular and a humoral arm. Components of humoral immunity include diverse molecular families, which represent functional ancestors of antibodies. They play key roles as effectors and modulators of innate resistance and inflammation. The long pentraxin PTX3 represents a prototype humoral effector molecule. Gene targeting of this evolutionarily conserved long pentraxin has unequivocally defined its role at the crossroads of innate immunity, inflammation, matrix deposition and female fertility. Here, we will review the studies on PTX3, which emphasize its role as a multifunctional soluble pattern recognition receptor acting as a non-redundant component of the humoral arm of innate immunity involved in fine-tuning inflammation, matrix deposition, angiogenesis and, in particular, in female fertility.