More than 250 tons of expired, surplus and redundant medicines worth £50m are returned to dispensing GP surgeries and pharmacies each year.
In addition, an unknown amount of medicine is disposed of incorrectly through household waste.
Dr Tony Jewell, Chief Medical Officer for Wales, and Paul Williams, the NHS chief executive, will write to health professionals to highlight the campaign.
They will remind them of the importance to prescribe only what is necessary to help patients manage their condition to avoid wasted medicines.
Health Minister Edwina Hart said: ‘Millions of pounds worth of waste medicines are being burnt every year. This is money that could be better spent elsewhere in the NHS.
‘Not only is there a significant cost associated with wasted medicines, if people have out-of-date medicines, they are risking their health.’
GP surgeries will be targeted with information leaflets as part of the campaign.
Patients receiving prescription medicines will be handed advice, such as ensuring they order the right amounts of medicines and do not stockpile drugs.