The prevalence of asthma has dramatically increased in recent decades. Exacerbations of asthma are a large contributor to asthma-related costs, and are primarily caused by viral and atypical bacterial infections. Rhinoviruses (RVs) are the most common viruses detected after an asthma exacerbation. RVs, respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) viral infections early in life can induce wheezing and are associated with the development of asthma later in life. Atypical bacterial infections from Mycoplasma pneumoniae and Chlamydia pneumoniae have also been linked to chronic asthma and potential asthma exacerbations. In this article, we will discuss recent developments in viral infections, specifically RV, RSV, and hMPV, and atypical bacterial infections as causes of asthma exacerbations, including new data focusing on the host immune response in airway epithelial cells and animal models of infection.