Mothers during lactation may encounter barriers including the need of medication intake due to a chronic or acute illness, which may affect mainly the duration of breastfeeding. In these cases, the issue of medication safety during lactation arises and maternal decisions usually depend on professional counseling. Providing scientifically valid information on the benefits of breastfeeding and the risk of exposure of the newborn/infant to medicines through breast milk is a responsibility of healthcare professionals. Reliable sources on the compatibility of medicines with breastfeeding vary and the information among them is conflicting or even insufficient, creating as a consequence difficulty for healthcare professionals to provide counseling. Given the fact that breastfeeding mothers are excluded from clinical trials as they are considered a vulnerable population, the scientific community has turned to alternative methods based on pharmacokinetic population modeling for medication safety during lactation. In addition, through pharmacovigilance science, databases related to drug compatibility with breastfeeding can be enriched with new data. Undoubtedly, the contribution of midwives and other healthcare professionals involved in breastfeeding plays a key role in the pharmacovigilance process through the observation and reporting of side effects. In the Greek national healthcare system, telephone helplines have been established to provide information on medication safety during lactation. Finally, information is provided on the guiding principles for midwives and other healthcare professionals regarding medication safety in breastfeeding mothers. The ultimate goal is to support and prolong breastfeeding with evidence-based knowledge.