Campaigners are calling for more treatment and research for those living with ME.
Many sufferers are under the age of 40, bed bound, weak, suffer with extreme tiredness, constant pain and are over sensitive to light and sound
It's thought that around 13,000 people in Wales have the condition.
The campaign group Millions Missing took to the streets of Cardiff as well as in more than 100 other cities across the world to demand change for people with Myalgic Encephalomyelitis (ME).
They say they want more spent on treatment and research.
Campaigners in Cardiff laid out shoes to represent sufferers who couldn't be there.
The Welsh Government said:
Health boards in Wales are responsible for the healthcare needs of their population as well as ensuring the correct level of healthcare professionals are appropriate. The NICE guidelines for the diagnosis and management of CFS/ME are currently under review and we would expect health boards to respond appropriately to any updates.
Emma-Jayne Lloyd, from Cardiff, had to quit her job as a teacher because of ME.
Watch her story below: