Wales' four police forces have clubbed together to distribute to pubs two million beer mats with eye-catching guidelines - designed to halt the practice.
Spike substances could include extra alcohol or even date-rape drugs.
Date rape drugs
While spiking is often meant as a prank, the consequences can be as serious as severe illness, assault or rape, police said.
Communities Minister Edwina Hart was at a press launch for the campaign.
"As we are approaching Christmas we must ensure that we raise awareness of the problems of spiked drinks," she said.
"It is vitally important that we protect our young people and also that they know how to protect themselves by being informed of the harm reduction message."
Five thousand cases of UK drug-rape were reported to the now-defunct National Drug Rape Trust over the last two years.
Campaigners say hundreds of women are raped each year after their drink or food is spiked with GHB and other drugs like Rohypnol.
Rape danger
Bought for as little as £5 on the internet or at sex shops, GHB is often taken as a "party drug" to intensify the effects of alcohol and as an aphrodisiac.
Also known as "liquid ecstasy", it was reclassified a Class "C" drug during the summer.
The Roofie Foundation, an advice group for drug-rape victims, said there were 876 cases of drug rape in 2000, a rise of 11% on the 778 cases in the previous year.
It estimates the number of victims in 2001 will show a slight increase to about 900 cases.