Excessive β-adrenergic receptor (βAR) stimulation and hyperactivation of the multifunctional Ca2+-calmodulin-dependent protein kinase II (CaMKII) play important roles in the initiation and maintenance of atrial fibrillation (AF), the world's most common cardiac arrhythmia. It has been postulated that the interplay of these two pathways with intracellular Ca2+ signaling drives a vicious cycle that promotes arrhythmogenesis. Here, we coupled our well-established computational model of human atrial cellular electrophysiology (extended to incorporate two recently-characterized atrial-predominant K+ currents) and Ca2+ handling (Grandi et al., 2011) with detailed descriptions of βAR/cAMP/PKA and CaMKII pathways (Soltis and Saucerman 2010; Morotti et al., 2014) to investigate their respective roles and potential synergy in promoting AF.