Nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) are activated upon engagement of a wide variety of immunoreceptors. Accumulating evidence has demonstrated that B-cell lymphoma 10 (BCL10) and mucosa-associated lymphoid tissue (MALT1) are essential signaling components for NF-κB and MAPK activation mediated by immunoreceptor tyrosine-based activation motif (ITAM)-coupled receptors in both adaptive and innate immunity. Recent studies have revealed that two caspase-recruitment domain (CARD) family adaptor molecules, CARD-containing MAGUK protein 1 (CARMA1) and CARD9, are crucial regulators of the ITAM-mediated signaling pathway by forming a complex with BCL10–MALT1 in lymphoid and myeloid cells, respectively. Here, we describe the immune responses and the cell-type-specific regulation mechanisms for NF-κB and MAPK activation controlled by CARMA1 and CARD9 through innate and adaptive immunoreceptors.