To examine whether ErbB signaling has a role in astrocytes of injured or diseased brains, we manipulated ErbB receptor activity in mature astrocytes by adopting a pan-ErbB strategy in mice. By conditionally expressing either a dominant-negative ErbB mutant that inhibited any ErbB receptor when coexpressed in the same cell or a constitutively active ErbB mutant that promoted ErbB receptor activation, we circumvented the limited information on ErbB receptor composition in astrocytes and focused on the function of ErbB signaling. Through in vivo studies combining loss- and gain-of-function approaches, we found that ErbB signaling positively regulated astrocyte reactivity, exerting a direct effect on hypertrophic remodeling and a cooperative effect on other features of reactive astrocytic responses.