All medicines have a shelf life, and the fate of expired medicines is an area of increasing concern. Despite the free returned medicine scheme available in Australia, many medicines are disposed of inappropriately or retained in the household beyond their expiry date. This is of particular concern for antimicrobials, where inappropriate disposal can lead to environmental contamination, and use outside of the prescribed need can potentially lead to poor clinical outcomes and antimicrobial resistance. Medicinal honey is increasingly acknowledged as a useful alternative to traditional antimicrobials. Honey is non-toxic, thereby avoiding the risk of environmental contamination, and there is no evidence of pathogens developing resistance to honey. However, there is a need for more evidence-based assessment of the potential of honey to promote its use in clinical practice. Here we examine 1) the shelf life of a set of native Australian honey samples following long term (15-17 years) storage by assessing their MICs against bacterial pathogens Staphylococcus aureus, Enterococcus faecalis and Pseudomonas aeruginosa and fungal pathogen Cryptococcus deuterogattii; 2) the presence of viable microbes in the stored honey; and 3) various components of the honey that may be responsible for activity. We find activity declines, but in most cases a useful level of antimicrobial activity is retained in honey stored for 15–17 years. Bacteria and yeasts could be cultured from most honey samples, with substantially less from those produced from Leptospermum plants. Levels of hydrogen peroxide production, phenolics, and antioxidants, along with colour intensity were all positively correlated with activity, but the extent varied with microbial species, and even when combined these had a relatively low predictive power for antimicrobial effect. We conclude that when stored appropriately honey has a good shelf life and it can suppress but not completely kill resident microbes. However, is difficult to predict the medicinal properties of most honey types using chemical assays alone, and these can only be reliably determined using bioassays such as the MIC.