Simple analgesics such as paracetamol or ibuprofen may be used for headache, myalgia (muscle pain) or fever, bearing in mind any contraindications or cautions. Ibuprofen has a slightly longer duration of action. If symptoms of pain or fever are particularly severe, ibuprofen and paracetamol may be used concomitantly, as there is some evidence of increased effectiveness according to a 2013 Cochrane review. Aspirin is no longer recommended as it is less well tolerated.

Some people find steam inhalation comforting in loosening mucus and relieving congestion, although a 2017 Cochrane review concluded there was no consistent evidence that this intervention worked. The BNF states that adding aromatic compounds such as menthol or eucalyptus oil may help, although there is little evidence of additional efficacy. The same is true of vapour rubs containing similar ingredients.

Saline nose drops or sprays can help liquefy mucus secretions so are another option for nasal congestion. In infants the drops or spray may help with feeding but some babies do not tolerate them. A 2015 Cochrane review found that in adults and children, saline nasal irrigation was safe, although sometimes associated with minor discomfort, but only with limited evidence of benefit.

Topical decongestants can have a role if nasal congestion is a problem. There is some evidence supporting the use of topical sympathomimetics, which work by constricting mucosal blood vessels, reducing oedema and facilitating drainage. They should only be used for a maximum of five to seven days due to the risk of secondary vasodilation and associated rhinitis medicamentosa (rebound congestion) upon stopping. According to the BNF, ephedrine is considered the safest sympathomimetic, with xylometazoline and oxymetazoline more likely to cause rebound congestion.

Oral decongestants such as pseudoephedrine and phenylephrine have little evidence but are included in many OTC cold remedies and, unlike their locally administered counterparts, are not associated with rebound congestion when stopped. Their sympathomimetic mode of action means they are not suitable for all and should be avoided by individuals taking monoamine oxidase inhibitors. Caution is needed in diabetes, hypertension, hyperthyroidism, prostatic hypertrophy, ischaemic heart disease or for individuals susceptible to closed-angle glaucoma. They can also be used as ingredients to manufacture drugs of abuse, so their sales are restricted; vigilance by pharmacy staff is important.

Antihistamines are included in some cold and flu remedies, the theory being that they help dry nasal secretions. A 2012 Cochrane review found that sedating antihistamines combined with a decongestant were effective, probably due to their anticholinergic effect, but side effects such as drowsiness, dry mouth, insomnia and dizziness are problematic, and there was no evidence of benefit in young children. There is no support for non-sedating antihistamines for colds or flu.

Cough medicines are commonly used. Expectorants such as ipecacuanha, guaifenesin and squill are intended to help cough up secretions. Demulcents such as glycerol, honey or syrup, can be used to soothe cough. Some contain ingredients intended as cough suppressants, such as codeine, dextromethorphan and pholcodine. A Cochrane review in 2014 showed no good evidence for or against these.