Cough and cold medications that contain nasal decongestants, antihistamines, cough suppressants, and expectorants commonly are used alone or in combination in attempts to temporarily relieve symptoms of upper respiratory tract infection in children aged <2 years. However, during 2004-2005, an estimated 1,519 children aged <2 years were treated in U.S. emergency departments for adverse events, including overdoses, associated with cough and cold medications. In response to reports of infant deaths after such events, CDC and the National Association of Medical Examiners (NAME) investigated deaths in U.S. infants aged <12 months associated with cough and cold medications. This report describes the results of that investigation, which identified deaths of three infants aged <6 months in 2005, for which cough and cold medications were determined by medical examiners or coroners to be the underlying cause. The dosages at which cough and cold medications can cause illness or death in children aged <2 years are not known. Food and Drug Administration (FDA)-approved dosing recommendations for clinicians prescribing cough and cold medications do not exist for this age group. Because of the risks for toxicity, absence of dosing recommendations, and limited published evidence of effectiveness of these medications in children aged <2 years, parents and other caregivers should not administer cough and cold medications to children in this age group without first consulting health-care provider and should follow the provider's instructions precisely. Clinicians should use caution when prescribing cough and cold medications to children aged <2 years. Moreover, clinicians should always ask caregivers about their use of over-the-counter combination medications to avoid overdose in children from multiple medications that contain the same ingredient.